MIC and time-kill study of antipneumococcal activities of RPR 106972 (a new oral streptogramin), RP 59500 (quinupristin-dalfopristin), pyostacine (RP 7293), penicillin G, cefotaxime, erythromycin, and clarithromycin against 10 penicillin-susceptible and -resistant pneumococci

Broth MICs and time-kill studies were used to test the activity of RP 59500 (quinupristin-dalfopristin), RPR 106972, pyostacine (RP 7293), erythromycin, clarithromycin, and cefotaxime for four penicillin-susceptible (MICs of 0.008 to 0.03 mu g/ml), two penicillin-intermediate (MIG of 0.25 mu g/ml), and four penicillin-resistant (MIG of 2.0 to 4.0 mu g/ml) strains of pneumococci: 6 of 10 strains were resistant to macrolides (MICs of greater than or equal to 0.5 mu g/ml). MICs of RP 59500 (0.5 to 1.0 mu g/ml), RPR 106972 (0.125 to 0.25 mu g/ml), and pyostacine (0.125 to 0.25 mu/ml) did not alter with the strain's penicillin or macrolide susceptibility status, Three penicillin-susceptible strains and one penicillin-intermediate strain were susceptible to macrolides (MICs of less than or equal to 0.25 mu g/ml); the macrolide MICs for the remaining strains were greater than or equal to 4.0 mu g/ml. Cefotaxime MICs rose with those of penicillin G, but all strains were inhibited at MICs of less than or equal to 2.0 mu g/ml. RP 59500 was bactericidal for all strains after 24 h at 2x MIC and yielded 90% killing of all strains at 6 h at 2x MIC; at 8x MIC, RP 59500 showed 90% killing of six strains within 10 min (approximately 0.2 h), In comparison, RPR 106972 was bactericidal for 9 of 10 strains at 2x MIC after 24 h and yielded 90% killing of all strains at 2x MIC after 6 h; 90% killing of six strains was found at 8x MIC at 0.2 h, Results for pyostacine were similar to those of RPR 106972, Erythromycin and clarithromycin were bactericidal for three of four macrolide-susceptible strains after 24 h at 4x MIG. Clarithromycin yielded 90% killing of three strains at 8x MIC after 12 h, Cefotaxime was bactericidal for all strains after 24 h at 4x MIG, yielding 90% killing of all strains after 6 h at 4x MIG. All three streptogramins yielded rapid killing of penicillin- and erythromycin-susceptible and -resistant pneumococci and were the only compounds which killed significant numbers of strains at 0.2 h.